Lacticaseibacillus rhamnosus attenuates gut-derived uremic toxins in patients with non-dialysis chronic kidney disease, partly through the anti-inflammatory molecules, impacts of innate immunity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Lacticaseibacillus rhamnosus attenuates gut-derived uremic toxins in patients with non-dialysis chronic kidney disease, partly through the anti-inflammatory molecules, impacts of innate immunity Asada Leelahavanichkul, Pornpimol Phuengmaung, Thansita Bhunyakarnjanarat, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6337297/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Because of the strain-dependent effect and the lack of simultaneous in vitro test with limited clinical data on Lacticaseibacillus rhamnosus L34 (L34) isolated from the Thai population, L34 was tested and compared with L. rhamnosus GG (LGG). The before and after test using L34 and a randomized placebo-controlled trial using placebo, L34, and LGG, for 4 weeks in patients with non-dialysis chronic kidney disease stage 3-5 (CKD) together with the in vitro experiments using indoxyl sulfate (IS, a representative uremic toxin) were performed. In comparison with the baseline, 4-week-L34 administration reduced gut-derived uremic toxins (GDUTs), except total IS and attenuated several biomarkers, including i) systemic inflammation, as measured by cytokines and neutrophils extracellular traps using citrullinated histone 3, cell-free DNA, and nuclear morphology fluorescent staining, ii) gut permeability defect (beta-d-glucan but not by endotoxemia), and iii) gut dysbiosis (fecal microbiome analysis). Additionally, L34-conditioned media attenuated IS-induced injuries on Caco-2 enterocytes, THP-1-derived-macrophages, and isolated neutrophils. Despite the possible different active compounds, both probiotics similarly attenuated IS-induced inflammation in vitro and in patients when compared with the placebo. Despite the possible different active molecules, L34 and LGG similarly attenuated systemic inflammation in patients with CKD, through the improved gut dysbiosis and anti-inflammation. Biological sciences/Immunology/Inflammation Biological sciences/Immunology/Innate immune cells Health sciences/Nephrology/Kidney diseases/Chronic kidney disease Lacticaseibacillus rhamnosus probiotics gut-derived uremic toxins gut leakage chronic kidney disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 30 May, 2025 Reviews received at journal 05 May, 2025 Reviews received at journal 05 May, 2025 Reviews received at journal 04 May, 2025 Reviewers agreed at journal 30 Apr, 2025 Reviewers agreed at journal 26 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 24 Apr, 2025 Editor assigned by journal 24 Apr, 2025 Editor invited by journal 22 Apr, 2025 Submission checks completed at journal 21 Apr, 2025 First submitted to journal 30 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6337297","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":448494886,"identity":"150fd113-cb45-4b05-bf23-5516877cbfa3","order_by":0,"name":"Asada Leelahavanichkul","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYDACdiB+wHAAzD7AUAEkmZkb8GthBuIEmJYDZ0AijCRoYTjYBiIJaOFvZj74IKHmjrzB8bMHD3+cVxvN3w7U8qNiG04tEofZkg0Sjj0z3HAmL+HAwW3Hc2ccZmxg7DlzG7c1h3nMJBLYDjPObMgxAGo5ltsA1MLM2IZbi/xh/u8/Ev4dtp/Z/waoZc6x3PmEtBgc5mFjSGw7nNgvAbKloSZ3AyEthofZjCUS+w4n90sAbTlz7EDuRqCWg/j8Ine8+eGHD98O27bx5xh/qKipy513/vDBBz8q8HgfDRwGkweIVg8EdaQoHgWjYBSMghECADdzZ7hXxl/WAAAAAElFTkSuQmCC","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":true,"prefix":"","firstName":"Asada","middleName":"","lastName":"Leelahavanichkul","suffix":""},{"id":448494889,"identity":"abc8bef1-091f-48fa-bd4d-132d479c4dc5","order_by":1,"name":"Pornpimol Phuengmaung","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Pornpimol","middleName":"","lastName":"Phuengmaung","suffix":""},{"id":448494891,"identity":"e10dd2fa-3596-47ea-9365-7d45bc8428d8","order_by":2,"name":"Thansita Bhunyakarnjanarat","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Thansita","middleName":"","lastName":"Bhunyakarnjanarat","suffix":""},{"id":448494893,"identity":"d98779c7-84eb-459c-810d-64e655284d57","order_by":3,"name":"Warerat Kaewduangduen","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Warerat","middleName":"","lastName":"Kaewduangduen","suffix":""},{"id":448494895,"identity":"de099a0d-b794-4ede-903e-25a350363cf1","order_by":4,"name":"Pimmada Boonnaj","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Pimmada","middleName":"","lastName":"Boonnaj","suffix":""},{"id":448494897,"identity":"6bfa9c09-f841-4904-a67b-52fb5548abe7","order_by":5,"name":"Pichanan Tengamnuay","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Pichanan","middleName":"","lastName":"Tengamnuay","suffix":""},{"id":448494898,"identity":"a603cac2-10e7-4916-a7cb-116c67fc51a2","order_by":6,"name":"Wiwat Chancharoenthana","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Wiwat","middleName":"","lastName":"Chancharoenthana","suffix":""},{"id":448494899,"identity":"1ce3225c-878f-4405-8f1c-86b9ab07d15a","order_by":7,"name":"Somkanya Tungsanga","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Somkanya","middleName":"","lastName":"Tungsanga","suffix":""},{"id":448494900,"identity":"eb978084-4ec6-4378-bc16-9565b8537cf2","order_by":8,"name":"Suwasin Udomkarnjananun","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Suwasin","middleName":"","lastName":"Udomkarnjananun","suffix":""},{"id":448494901,"identity":"b5ffa27f-5b74-45c4-b277-56e17c27b8c1","order_by":9,"name":"Somying Tumwasorn","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Somying","middleName":"","lastName":"Tumwasorn","suffix":""}],"badges":[],"createdAt":"2025-03-30 07:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6337297/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6337297/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-12768-z","type":"published","date":"2025-07-31T16:05:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82136826,"identity":"4c266480-180a-400c-8d08-7218750b36cc","added_by":"auto","created_at":"2025-05-07 06:15:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3135351,"visible":true,"origin":"","legend":"\u003cp\u003eThe characteristics of patients with chronic kidney disease (CKD) at before and after\u003c/p\u003e\n\u003cp\u003e4 week of L. rhamnosus L34 (L34) administration, as indicated by hemoglobin, blood urea\u003c/p\u003e\n\u003cp\u003enitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR), urine protein\u003c/p\u003e\n\u003cp\u003ecreatinine ratio (UPCI) (A-E), serum cytokines (TNF-α, IL-6, and IL-10) (F-H), gut-derived\u003c/p\u003e\n\u003cp\u003euremic toxins (free indoxyl sulfate, total indoxyl sulfate, and p-cresol) (I-K), endotoxemia (L),\u003c/p\u003e\n\u003cp\u003eserum (1→3)-beta-D-glucan (BG) (M), neutrophil extracellular traps (NETs), as determined by\u003c/p\u003e\n\u003cp\u003enuclear morphology with representative fluorescent pictures (N, O), cell-free DNA (P),\u003c/p\u003e\n\u003cp\u003ecitrullinated histone 3 (CitH3) (Q), the selected graph presentation of fecal bacterial abundance\u003c/p\u003e\n\u003cp\u003e(phylum and genus levels) from fecal microbiome analysis (R-X), and fecal fungal abundance\u003c/p\u003e\n\u003cp\u003e(expressing in cycle threshold or Ct) (Y), are demonstrated (n = 10/group). *, p \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/d9570ba63b94ec2b06dbd113.png"},{"id":82136835,"identity":"770fcdf5-1ba7-4d99-837b-2d476d7a9316","added_by":"auto","created_at":"2025-05-07 06:15:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36974422,"visible":true,"origin":"","legend":"\u003cp\u003eThe fecal microbiome analysis of patients with chronic kidney disease (CKD) at\u003c/p\u003e\n\u003cp\u003ebefore and after 4 weeks of L. rhamnosus L34 (L34) administration as indicated by the\u003c/p\u003e\n\u003cp\u003eabundance of bacteria in phylum, class, order, family, genus, and species is demonstrated (n =\u003c/p\u003e\n\u003cp\u003e10/group).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/0b793c8a5a266d8c598322e4.png"},{"id":82136831,"identity":"2996e325-6bca-4415-be2c-43bd73664a74","added_by":"auto","created_at":"2025-05-07 06:15:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":16409481,"visible":true,"origin":"","legend":"\u003cp\u003eThe fecal microbiome analysis of patients with chronic kidney disease (CKD) at\u003c/p\u003e\n\u003cp\u003ebefore and after 4 week of L. rhamnosus L34 (L34) administration as indicated by the\u003c/p\u003e\n\u003cp\u003eCladogram (a branching diagram showing the cladistic relationship among species) (A), the\u003c/p\u003e\n\u003cp\u003eLinear discriminant analysis Effect Size (LEfSe) (the identified bacteria characterizing the\u003c/p\u003e\n\u003cp\u003edifferences between groups) (B), and the principal coordinate analysis (PCoA) (the\u003c/p\u003e\n\u003cp\u003evisualization indicating the differences between microbial communities by projecting data onto\u003c/p\u003e\n\u003cp\u003ea 2 dimensional plot) on Bray-Curtis (C) are demonstrated\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/f944ab827a12c2ecc18af22c.png"},{"id":82136829,"identity":"f53a01fc-406c-4897-99b1-631c1015cec4","added_by":"auto","created_at":"2025-05-07 06:15:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4648641,"visible":true,"origin":"","legend":"\u003cp\u003eThe characteristics of different cells after the 24 h incubation by the control culture\u003c/p\u003e\n\u003cp\u003emedia (Control) or Lacticaseibacillus condition media from L. rhamnosus L34 (LCM) or\u003c/p\u003e\n\u003cp\u003eindoxyl sulfate (IS) or IS with LCM (IS+LCM) are demonstrated. For enterocytes (Caco-2\u003c/p\u003e\n\u003cp\u003ecells), supernatant IL-8 (A), the expression of several genes, including IL-8, NF-κB, MUC-2,\u003c/p\u003e\n\u003cp\u003eand occludin (B-E), and transepithelial electrical resistance (TEER) (F) are indicated. For THP-\u003c/p\u003e\n\u003cp\u003e1-derived-macrophages (THP-1), supernatant cytokines (TNF-α, IL-6, and IL-10) (G-I) and\u003c/p\u003e\n\u003cp\u003ethe expression of several genes, including NF-κB and NOS2 (J, K), are used. For neutrophils,\u003c/p\u003e\n\u003cp\u003ethe neutrophil extracellular traps (NETs), as determined by nuclear morphology with\u003c/p\u003e\n\u003cp\u003erepresentative fluorescent pictures (L, M), cell-free DNA (N), citrullinated histone 3 (CitH3)\u003c/p\u003e\n\u003cp\u003e(O), are shown. The results were retrieved from the isolated triplicated experiments. #, p \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003evs. Control, *, p \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/0f9a615ed916a5b10faffa1c.png"},{"id":82138318,"identity":"f83fd7b5-faa7-41b9-b90a-e075131d685d","added_by":"auto","created_at":"2025-05-07 06:23:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":920910,"visible":true,"origin":"","legend":"\u003cp\u003eThe characteristics of enterocytes (Caco-2 cells), THP-1-derived-macrophages\u003c/p\u003e\n\u003cp\u003e(THP-1), and neutrophils after 24 h incubation with indoxyl sulfate (IS) together with the\u003c/p\u003e\n\u003cp\u003eLacticaseibacillus condition media (LCM) from L. rhamnosus L34 (LCM from L34) or from\u003c/p\u003e\n\u003cp\u003eL. rhamnosus GG (LCM from LGG) after neutralizing by several enzymes, including α-\u003c/p\u003e\n\u003cp\u003eamylase (Amy), lipase (Lip), protease (Pro), and lysozyme (Lyz), or no enzyme (non) in\u003c/p\u003e\n\u003cp\u003ecomparison with the control media (no LCM), as demonstrated by supernatant IL-8 for Caco-\u003c/p\u003e\n\u003cp\u003e2 (A), supernatant IL-6 for THP-1 (B), and citrullinated histone 3 (CitH3) for neutrophils (C),\u003c/p\u003e\n\u003cp\u003eare demonstrated. The results were retrieved from the isolated triplicated experiments. #, p \u0026lt;\u003c/p\u003e\n\u003cp\u003e0.05 vs. No LCM.\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/6312c1bf0bb5deaff40c191b.png"},{"id":82136825,"identity":"9832bb5b-fc20-4fbd-9b2e-98e557da61bc","added_by":"auto","created_at":"2025-05-07 06:15:17","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":178478,"visible":true,"origin":"","legend":"\u003cp\u003eSchema of the cross-sectional analysis and the characteristics of patients with chronic\u003c/p\u003e\n\u003cp\u003ekidney disease (CKD) after 4 week administration of L. rhamnosus L34 (L34) or L. rhamnosus\u003c/p\u003e\n\u003cp\u003eGG (LGG) or placebo control (placebo) is demonstrated.\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/8a57833e8a0fafb34d520ce7.png"},{"id":82136832,"identity":"a2884728-ad63-48ae-aacf-ac153e4a42c0","added_by":"auto","created_at":"2025-05-07 06:15:17","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":2623438,"visible":true,"origin":"","legend":"\u003cp\u003eThe characteristics of participants after the randomized control trial and the\u003c/p\u003e\n\u003cp\u003echaracteristics of patients with chronic kidney disease (CKD) after 4 week administration of L.\u003c/p\u003e\n\u003cp\u003erhamnosus L34 (L34) or L. rhamnosus GG (LGG) or placebo control (placebo), as indicated\u003c/p\u003e\n\u003cp\u003eby hemoglobin, blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration\u003c/p\u003e\n\u003cp\u003erate (eGFR), urine protein creatinine ratio (UPCI) (A-E), serum cytokines (TNF-α, IL-6, and\u003c/p\u003e\n\u003cp\u003eIL-10) (F-H), gut-derived uremic toxins (free indoxyl sulfate, total indoxyl sulfate, and p-\u003c/p\u003e\n\u003cp\u003ecresol) (I-K), endotoxemia (L), serum (1→3)-beta-D-glucan (BG) (M), cell-free DNA (N), and\u003c/p\u003e\n\u003cp\u003ecitrullinated histone 3 (CitH3) (O) are demonstrated (n = 25/group). *, p \u0026lt; 0.05 vs. placebo.\u003c/p\u003e","description":"","filename":"Fig7.png","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1/7fd6ff295a61d9709356d488.png"},{"id":88268404,"identity":"ef3e5923-f497-4d09-8448-7229d1625af8","added_by":"auto","created_at":"2025-08-04 16:51:31","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8045959,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6337297/v1_covered_199a3cd8-4a4c-4d40-986d-d53b19c642b4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lacticaseibacillus rhamnosus attenuates gut-derived uremic toxins in patients with non-dialysis chronic kidney disease, partly through the anti-inflammatory molecules, impacts of innate immunity ","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":" Lacticaseibacillus rhamnosus, probiotics, gut-derived uremic toxins, gut leakage, chronic kidney disease","lastPublishedDoi":"10.21203/rs.3.rs-6337297/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6337297/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Because of the strain-dependent effect and the lack of simultaneous in vitro test with limited clinical data on Lacticaseibacillus rhamnosus L34 (L34) isolated from the Thai population, L34 was tested and compared with L. rhamnosus GG (LGG). The before and after test using L34 and a randomized placebo-controlled trial using placebo, L34, and LGG, for 4 weeks in patients with non-dialysis chronic kidney disease stage 3-5 (CKD) together with the in vitro experiments using indoxyl sulfate (IS, a representative uremic toxin) were performed. In comparison with the baseline, 4-week-L34 administration reduced gut-derived uremic toxins (GDUTs), except total IS and attenuated several biomarkers, including i) systemic inflammation, as measured by cytokines and neutrophils extracellular traps using citrullinated histone 3, cell-free DNA, and nuclear morphology fluorescent staining, ii) gut permeability defect (beta-d-glucan but not by endotoxemia), and iii) gut dysbiosis (fecal microbiome analysis). Additionally, L34-conditioned media attenuated IS-induced injuries on Caco-2 enterocytes, THP-1-derived-macrophages, and isolated neutrophils. Despite the possible different active compounds, both probiotics similarly attenuated IS-induced inflammation in vitro and in patients when compared with the placebo. Despite the possible different active molecules, L34 and LGG similarly attenuated systemic inflammation in patients with CKD, through the improved gut dysbiosis and anti-inflammation.","manuscriptTitle":"Lacticaseibacillus rhamnosus attenuates gut-derived uremic toxins in patients with non-dialysis chronic kidney disease, partly through the anti-inflammatory molecules, impacts of innate immunity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 06:15:12","doi":"10.21203/rs.3.rs-6337297/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-30T11:38:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T12:46:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T08:51:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-04T16:39:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310137960993341155430138731165574100703","date":"2025-04-30T06:29:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6054287422140012620246929753674508553","date":"2025-04-27T02:03:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"183963629295773385532313270224539845867","date":"2025-04-24T16:09:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313349103888468403641491866090699880061","date":"2025-04-24T11:30:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-24T10:03:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-24T09:53:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-22T05:33:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-21T05:41:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-30T07:24:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"af269df2-142f-4c10-a2d1-4324fa4c114e","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":47731055,"name":"Biological sciences/Immunology/Inflammation"},{"id":47731056,"name":"Biological sciences/Immunology/Innate immune cells"},{"id":47731057,"name":"Health sciences/Nephrology/Kidney diseases/Chronic kidney disease"}],"tags":[],"updatedAt":"2025-08-04T16:42:28+00:00","versionOfRecord":{"articleIdentity":"rs-6337297","link":"https://doi.org/10.1038/s41598-025-12768-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-31 16:05:27","publishedOnDateReadable":"July 31st, 2025"},"versionCreatedAt":"2025-05-07 06:15:12","video":"","vorDoi":"10.1038/s41598-025-12768-z","vorDoiUrl":"https://doi.org/10.1038/s41598-025-12768-z","workflowStages":[]},"version":"v1","identity":"rs-6337297","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6337297","identity":"rs-6337297","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.